fumarate hydratase Lentiviral Activation Particles (h): sc-401660-LAC

Human FH encodes fumarate hydratase, a mitochondrial enzyme that catalyzes the reversible hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle, linking oxidative metabolism to cellular redox balance. FH activity supports anaplerosis, NADH production, and coordination of mitochondrial function with cytosolic metabolic programs. Perturbation of FH can drive fumarate accumulation that impacts hypoxia signaling, epigenetic regulation, and stress-response pathways through altered metabolite-dependent enzyme activities. Consequently, FH is widely studied in the context of metabolic rewiring and tumor biology, as well as in inherited metabolic disease models affecting energy homeostasis.

fumarate hydratase Lentiviral Activation Particles (h) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient FH upregulation across a broader range of human cell types.

fumarate hydratase Lentiviral Activation Particles (h) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the FH transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous fumarate hydratase expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native FH genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.